Slide 1: Clinical Results and Plan Forward: SRP-1001 and SRP-1003
Clinical Results and Plan Forward: SRP-1001 for Facioscapulohumeral Muscular Dystrophy Type 1 (FSHD1) SRP-1003 for Myotonic Dystrophy Type 1 (DM1) March 25, 2026 ©SAREPTA THERAPEUTICS, INC. 2026. ALL RIGHTS RESERVED. 1
Slide 2: Today's Speakers
Today’s Speakers Doug Ingram Louise Rodino-Klapac, PhD James Richardson, Ian Estepan Rachael Potter, PhD Chief Executive Officer President, MA (Oxon), BMBCh, President, Senior Vice President, R&D and Technical Operations Chief Operating Officer Chief Scientific Officer MBA, MRCP (Lon) Executive Vice
Slide 3: Opening Remarks
Opening Remarks Doug Ingram Chief Executive Officer ©SAREPTA THERAPEUTICS, INC. 2026. ALL RIGHTS RESERVED. 3
Slide 4: Forward-looking statements
Forward-looking statements This presentation contains forward-looking statements. Any statements contained in this presentation that are not statements of historical fact may be deemed to be forward-looking statements. Words such as "believes," "anticipates," "plans," "expects," "will," "intends," "
Slide 5: Strengthening Sarepta's commitment to and leadership position in rare, neuromuscular diseases
Strengthening Sarepta’s commitment to and leadership position in rare, neuromuscular diseases ©SAREPTA THERAPEUTICS, INC. 2026. ALL RIGHTS RESERVED. 5
Slide 6: Early clinical data strengthen potential best-in-class approach for SRP-1001 and SRP-1003
Early clinical data strengthen potential best-in-class approach for SRP-1001 and SRP-1003 to treat FSHD1 and DM1 • Maximizing Therapeutic Delivery and Effect to Muscle – Clinical experience to date matches animal-model data: The TRiMTM platform’s αvβ6 integrin-targeting ligand drives potentially gre
Slide 7: Differentiated Integrin-Based Delivery Technology
Differentiated Integrin-Based Delivery Technology: Targeting the Biological Root Cause of Disease Louise Rodino-Klapac, PhD President, R&D and Technical Operations ©SAREPTA THERAPEUTICS, INC. 2026. ALL RIGHTS RESERVED. 7
Slide 8: Components of TRiM and the science that enables our pipeline
Components of TRiMTM and the science that enables our pipeline Linker Delivery Designed to provide Tissue-specific ligands stability/orientation. Linker is (peptide, small molecule, Ab) selected to optimize efficacy, designed to deliver siRNA to reduce tox, and CMC Liver, CNS, Muscle, Heart etc. com
Slide 9: Distinct Mechanism of Action: siRNA-mediated mRNA degradation
Distinct Mechanism of Action: siRNA-mediated mRNA degradation designed to enable specific target knockdown 2 siRNA has been modified to preferentially load the guide strand leading to enhanced specificity 3 Complementary pairing 4 Catalytically active RISC cleaves multiple target mRNAs, resulting in
Slide 10: Targeting αvβ6 integrin over TfR1 for greater muscle uptake
Targeting αv6 integrin over TfR1 for greater muscle uptake High expression and surface availability of αv6 in muscle make it an ideal receptor for targeted siRNA delivery TfR1 s : 5%1 of receptors available for binding on surface at any one time; majority are intracellular IV Delivery αv6: ~40%3
Slide 11: Potential advantages of siRNA integrin approach
Potential advantages of siRNA integrin approach and best-in-class therapies to treat FSHD1 and DM1 Better delivery to muscle with integrin αv6 Optimal clinical impact αv6 siRNA TfR1mAb TfR1fAb siRNA ASO Potency Better muscle penetration (e.g., delivers more Rx to muscle) Safety and lack of dose li
Slide 12: Pre-clinical in-vivo dose-dependent increase in plasma exposure
Pre-clinical in-vivo dose-dependent increase in plasma exposure via the TRiMTM platform The dose-dependent increase and absence of saturation in NHP plasma exposure (up to 26 mg/kg siRNA dose) provide a clear path to increased muscle delivery and stronger pharmacodynamic activity for both SRP-1001 a
Slide 13: Pre-clinical in-vivo muscle siRNA delivery and mRNA knock-down
Pre-clinical in-vivo muscle siRNA delivery and mRNA knock-down via the TRiMTM platform The linear increase in SRP-1003 plasma exposure translated into enhanced and dose-dependent muscle drug delivery, driving robust target engagement through maximal DMPK mRNA knockdown in NHPs ©SAREPTA THERAPEUTICS,
Slide 14: Clinical Results: SRP-1001 (FSHD1)
Clinical Results: SRP-1001 (FSHD1) James Richardson, MA (Oxon), BMBCh, MBA, MRCP (Lon) Executive Vice President, Chief Medical Officer ©SAREPTA THERAPEUTICS, INC. 2026. ALL RIGHTS RESERVED. 14
Slide 15: Safety, Delivery to muscle, Impact on disease pathways
Delivery Impact on Safety to muscle disease pathways ©SAREPTA THERAPEUTICS, INC. 2026. ALL RIGHTS RESERVED. 15
Slide 16: FSHD: Multiple skeletal muscles affected, beginning with the face
FSHD FSHD: Multiple skeletal muscles affected, beginning with the face Facial Muscles Scapular Girdle Muscles Upper Limb Muscles Abdominal Muscles Pelvic Girdle Muscles Muscle Weakness and Mobility • ~50% of FSHD patients will progress to becoming dependent on a wheelchair after ~20 years • >50% of
Slide 17: FSHD is caused by the contraction of the D4Z4 repeat
FSHD FSHD is caused by the contraction of the D4Z4 repeat, leading to the abnormal expression of DUX4, which is typically silenced early in life DUX4 Gene Expression A DUX4 Transcription Factor B FSHD genotype leads to aberrant DUX4 expression C Downstream Cellular Consequences ©SAREPTA THERAPEUTICS
Slide 18: Study SRP-1001-101: Phase 1/2 trial in FSHD1
FSHD Study SRP-1001-101: A phase 1/2 randomized, placebo-controlled trial in participants aged 16-70 with FSHD1 Part 1: SAD Part 2: MAD D1 Day 42 Day 90 D1 3M 6M 9M 12M Biopsy (Bx) Bx EOS Bx Bx EOS Cohort Design Endpoints SAD MAD C1-4: n=6, 2:1 C5-7: n up to 12, 3:1 Primary: • Functional: RWS, 6MWT,
Slide 19: Baseline characteristics
FSHD Baseline characteristics SAD MAD Overall Cohort 1 Cohort 2 Cohort 3 Cohort 4 Cohort 5 Cohort 6 Pooled Placebo Treated Total (1.02 mg/kg) (2.04 mg/kg) (4.08 mg/kg) (8.17 mg/kg) (4.08 mg/kg) (8.17 mg/kg) N=16 N=40 N=56 N=5 N=4 N=4 N=5 N=11 N=11 Age (years) 36.2 (14.15) 49.0 (6.00) 42.8 (9.29) 34.
Slide 20: SRP-1001 shows consistent dose-dependent increase in plasma exposure
FSHD SRP-1001 shows consistent dose-dependent increase in plasma exposure up to the highest dose cohort tested so far Plasma Exposure by Dose Level Dose-dependent increase in plasma AUC up to 8 mg/kg, representing the highest siRNA dose evaluated to date for FSHD SRP-1001 siRNA dose AUC = area under
Slide 21: Single dose of SRP-1001 delivers 6-fold greater siRNA muscle concentration
FSHD Single dose of SRP-1001 delivers 6-fold greater siRNA muscle concentration than multiple doses of transferrin-targeting ligand SRP-1001 Muscle Concentration by Dose Level • Dose-dependent increase in muscle concentration up to 4.08 mg/kg, representing the highest siRNA 28.4 nM dose with muscle
Slide 22: SRP-1001 suppresses DUX4-regulated genes after a single dose
FSHD SRP-1001 suppresses DUX4-regulated genes after a single dose -90% -90% -93% SRP-1001 treatment cohorts pooled from siRNA dose cohort 1 (1.02 mg/kg), cohort 2 (2.04 mg/kg), and cohort 3 (4.08 mg/kg). • *qPCR composite scores for CS4 (MBD3L2, TRIM43, KHDC1L, LEUTX), CS6 (MBD3L2, KHDC1L, CCNA1, PR
Slide 23: SRP-1001 drives rapid reduction in serum creatine kinase
FSHD SRP-1001 drives rapid reduction in serum creatine kinase (CK) with a single dose of SRP-1001 SRP-1001 achieved a 33% reduction in CK vs placebo at Day 42 SRP-1001 -33% SRP-1001 0 15 30 42 60 75 90 Days Data represent mean percent change from baseline ± SEM. Placebo (n = 16) and SRP-1001 treatme
Slide 24: SRP-1001-101: Reassuring safety profile to date
FSHD SRP-1001-101: Reassuring safety profile to date with no serious related TEAEs SAD (Active and Placebo) MAD (Active and Placebo) Overall Cohort 1 Majority of TEAEs were mild to moderate Cohort 2 Cohort 3 Cohort 4 Cohort 5 Cohort 6 in severity (1.02 Total (2.04 mg/kg) (4.08 mg/kg) (8.17 mg/kg) (4
Slide 25: Clinical Results: SRP-1003 (DM1)
Clinical Results: SRP-1003 (DM1) James Richardson, MA (Oxon), BMBCh, MBA, MRCP (Lon) Executive Vice President, Chief Medical Officer ©SAREPTA THERAPEUTICS, INC. 2026. ALL RIGHTS RESERVED. 25
Slide 26: DM1: A multi-system disorder
DM1 DM1: A multi-system disorder impacting skeletal and smooth muscle along with other organs Fatigue, apathy, cognitive impairment Frontal balding Cataracts Facial muscle weakness; TMJ dysfunction Respiratory failure (skeletal muscle weakness Cardiac conduction abnormalities (bradyarrythmias and CN
Slide 27: DM1: Expanded DMPK repeat, leading to multi-system impact
DM1 DM1: Expanded DMPK repeat, leading to multi-system impact Targeting and knockdown of DMPK MUST occur in nucleus for therapeutic benefit DM1 Genetic Cause DMPK DNA Expanded tri-nucleotide repeat in the DMPK gene (CTG)n (50 – 1000 repeats) 5’CAP AAAAA RNA Repeats accumulate in the nucleus and crea
Slide 28: Study SRP-1003-101: Phase 1/2 trial in DM1
DM1 Study SRP-1003-101: A phase 1/2 randomized, placebo-controlled trial in participants aged 18-65 with DM1 Part 1: SAD Part 2: MAD D1 D30 Day 90 D1 D30 D90/71 D120/100 D180/140 Biopsy (Bx) Bx Bx/EOS Bx Bx Bx EOS Cohort Design Endpoints SAD MAD Primary: • Functional (secondary in Cohort 1 Cohort 3
Slide 29: Baseline characteristics
DM1 Baseline characteristics SAD MAD Cohort 1 Cohort 2 Cohort 3 Cohort 4 Placebo Total (1.02 mpkg) (2.04 mpkg) (<=3.07 mpkg) (<=4.10 mpkg) N=11 N=36 N=10 N=6 N=5 N=4 Mean (sd) or Freq (%) Age (years) 39.2 (11.84) 36.0 (9.06) 47.0 (12.04) 41.8 (7.09) 36.3 (9.16) 39.1 (10.32) Female, n (%) 6 (60.0) 1
Slide 30: SRP-1003 shows dose-dependent increase in plasma exposure
DM1 SRP-1003 shows dose-dependent increase in plasma TM exposure, reinforcing cross-program consistency in the TRiM platform Plasma Exposure by Dose Level Dose-dependent increase in plasma AUC up to 3.07 mg/kg, representing the highest SRP-1003 dose cohort with data to date SRP-1003 siRNA dose AUC =
Slide 31: Superior muscle delivery with a single low dose of SRP-1003
DM1 Superior muscle delivery with a single low dose of SRP-1003 SRP-1003 Muscle Concentration • SRP-1003 in the lowest dose cohort SRP-1003 (1.02 siRNA mg/kg) mediates robust 12.2 nM siRNA delivery into the muscle (single lowest dose) • A single low dose of SRP-1003 significantly outperforms repeate
Slide 32: SRP-1003-101: Reassuring safety profile to date
DM1 SRP-1003-101: Reassuring safety profile with no serious related TEAEs to date SAD (Active and Placebo) MAD (Active and Placebo) Overall Majority of TEAEs were mild to moderate in severity Cohort 1 Cohort 2 Cohort 3 Cohort 6 • Three serious TEAEs in 2 subjects Total (1.02 mg/kg) (2.04 mg/kg) (≤3.
Slide 33: Conclusions from clinical data to date
Conclusions from clinical data to date • Well-tolerated with no dose-limiting toxicity allowing us to continue dose escalating and the potential to drive differentiated efficacy • Superior muscle concentration • Successful target engagement with emerging biomarker evidence of potentially meaningful
Slide 34: Closing Remarks
Closing Remarks Doug Ingram Chief Executive Officer ©SAREPTA THERAPEUTICS, INC. 2026. ALL RIGHTS RESERVED. 34
Slide 35: siRNA Pipeline
DISCOVERY/PRECLINICAL CLINICAL siRNA U.S. patient prevalence αv 6 integrin peptide MUSCLE SRP-1001 Facioscapulohumeral muscular dystrophy, Type 1 (FSHD1) ~16,0001 Pipeline SRP-1003 LUNG Myotonic dystrophy, Type 1 (DM1) ~40,0002 SRP-1002 Idiopathic pulmonary fibrosis (IPF) ~60,0003 CNS SRP-1004 Spin
Slide 36: siRNA Programs: Upcoming milestones over the next 12–18 Months
siRNA Programs: Upcoming milestones over the next 12 – 18 Months SRP-1001 SRP-1003 SRP-1005 FSHD1 DM1 Huntington’s MAD study data MAD study data Commence dosing – 2H 2026 – 2H 2026 – 1H 2026 Casi22 data Proof-of-biology data – 2H 2026 – 1H 2027 ©SAREPTA THERAPEUTICS, INC. 2026. ALL RIGHTS RESERVED.
Slide 37: Clinical Results and Plan Forward: SRP-1001 and SRP-1003
Clinical Results and Plan Forward: SRP-1001 for Facioscapulohumeral Muscular Dystrophy Type 1 (FSHD1) SRP-1003 for Myotonic Dystrophy Type 1 (DM1) March 25, 2026 ©SAREPTA THERAPEUTICS, INC. 2026. ALL RIGHTS RESERVED. 37